Deletion of 5q, del(5q)
Partial or complete deletion of the long arm of chromosome 5 [del(5q)], with or without additional karyotypic abnormalities, is present in 10-15% of myelodysplastic syndromes (MDS). Anemia in these MDS responds less often to erythroblastic stimulating agents. However, immunomodulatory, anti-cytokine, and anti-angiogenic agent Lenalidomide (CC5013) leads to red blood cells transfusion independence of low risk MDS with del(5q).
The addition of lenalidomide inhibits the in vitro proliferation of erythroblasts harboring del(5q) while the proliferation of cells from normal controls and cells without 5q deletion is not affected. Patients with mutated TP53 show poorer erythroid and cytogenetic responses to lenalidomide and a higher potential for acute myeloid leukemia (AML) evolution. The mechanism of lenalidomide action is different in non-del(5q) MDS, where lenalidomide restores and promotes effective erythropoiesis without direct cytotoxic effect.
The low risk del(5q) MDS is now recognized as a distinct pathologic subtype of MDS with markedly better clinical responses with lenalidomide treatment compared to non del(5q) MDS patients. With the supportive therapy, the prognosis of 5q- syndrome is favorable, with reported median survival ranging from 53 to 146 months. MDS with 5q- as part of a complex karyotype (3 or more abnormalities) have an unfavorable prognosis.
